Practical RetinaIncorporating current trials and technology into clinical practice

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Evaluation of the Retinal and Choroidal Vasculature With OCT Angiography Versus Conventional Angiographyby Colin S. Tan, MBBS, MMed (Ophth), FRCSEd (Ophth), Louis W. Lim, MBBS, and SriniVas R. Sadda, MD

The role of optical coherence tomogra-phy angiography (OCTA) in the evalu-ation of the retinal and choroidal vas-culature is still evolving as we learn more about this fascinating technolo-

gy. Since 2015, we have seen numer-ous papers pub-lished comparing OCTA to conven-tional fluorescein angiography (FA) and indocyanine green angiography (ICGA) to evalu-ate various disease states. Retina spe-cialists are trying

to process this flood of data as we lack a review of the literature regarding this topic.

I asked Colin S. Tan, MBBS, MMed (Ophth), FRCSEd (Ophth), Louis W. Lim, MBBS, and SriniVas R. Sadda, MD, to provide us with an overview of the merits of each OCTA, FA, and ICGA in evaluating various retinal and choroidal diseases as well as oth-er widely recognized retinal vascular features. They will also summarize for us the pros and cons of each of the three angiography methods.

Obviously, OCTA is a very useful technology and its role will only in-crease as advances in processing algo-rithms continue. The insights and ex-pertise that Drs. Tan, Lim, and Sadda share with us will be very helpful as we apply OCTA into our clinical prac-tices.

Optical coherence tomography angiography (OCTA) is an exciting new technology that promises to revolutionize the imaging of patients with various ocular conditions. OCT scans provide high-resolution structural detail of the retina and choroid. In contrast, OCTA allows visualization of blood flow within the layers of the retina and choriocapillaris.1,2

OCTA is based on the premise that blood corpuscles are moving within retinal vessels, whereas the surrounding structures are not.1,2

Stationary tissue shows high correlation in imaging characteristics from one frame to the next, whereas blood flowing through vessels causes changes in reflectance over time and localized areas of low correlation between frames. The motion of blood within vessels can be detected using phase/Doppler shift, amplitude variation, or a combination of these. OCTA uses rapidly performed OCT B-scans at the same location to analyze for variation, and processing algorithms then create vascular flow maps of the region.

The advantage of OCTA is that it is a rapid, noninvasive, dyeless system that allows simultaneous assessment of structure and flow with better microvascular and depth resolution than conventional angiograms. In contrast, conventional angiograms require intravenous access, and fluorescein and indocyanine

Colin S. Tan

Louis W. Lim

SriniVas R. Sadda

doi: 10.3928/23258160-20161130-01

Seenu M. Hariprasad

Practical Retina

Co-Editor

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green dyes may cause allergic reactions.1,3 OCTA is also faster and cheaper, and hence can be performed more frequently compared to conventional angiograms.

Since its introduction, OCTA has been applied to the management of many common retinal conditions.

AGE-RELATED MACULAR DEGENERATION

In neovascular age-related macular degeneration (AMD), choroidal neovascularization (CNV) lesions

are traditionally imaged using fluorescein angiography (FA) and indocyanine green angiography (ICGA). OCTA is useful in detecting the CNV lesion (Figure 1) and monitoring its progress during treatment. In one study, CNV lesions were reported to have been detected in 64.4% of eyes when compared to FA.4 On OCTA, the CNV lesions are located in the outer retina and choriocapillaris layers (Figure 1B),5 consistent with the pathophysiology of the disease. In contrast,

Figure 1. Age-related macular degeneration. (A) Fluorescein angiogram demonstrating leakage consistent with ocular choroidal neovas-cularization (CNV) superior to the fovea. (B) Optical coherence tomography angiography (OCTA) of the choriocapillaris layer demonstrat-ing CNV. (C) Indocyanine green angiography with the CNV net visible superior to the fovea. (D) OCT illustrating elevation of the retinal pigment epithelium with subretinal fluid and intraretinal cysts.

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the superficial and deep retinal vascular plexuses appear normal.

Nomenclature for CNV LesionsAlthough a consensus nomenclature is currently

lacking, several patterns of CNV have been described,6 including:

• Well-defined patterns, which may be lacy-wheel or sea-fan shaped.

• Long, filamentous linear vessels.• “Medusa”: The vessels arise from a large

main trunk, and branch in all directions from this location.

• “Seafan”: A large main trunk or feeder

Figure 2. Diabetic retinopathy and macular edema. (A) Optical coherence tomography angiography (OCTA) of the superficial retinal plexus illustrating areas of capillary dropout throughout the macula. The foveal avascular zone is irregular and disrupted. (B) OCTA of the deep capillary plexus illustrating regions of capillary dropout. Microaneurysms are seen superior and temporal to the fovea. (C) Vessel density map of the superficial retinal plexus. Regions of capillary dropout seen in Figure 2A are reflected as areas of reduced or absent vessels, which appear as dark blue on the density map. (D) OCT scan illustrating intraretinal cysts and retinal edema temporal to the fovea.

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vessel is seen, but the majority of the CNV membrane radiates in one direction.

• Glomerulus shape.• A “dead tree” appearance.

Prognostic IndicatorsThe pattern of the CNV lesion may be of prognostic

significance. A study of 80 eyes reported that among eyes that clinicians judged to require treatment based on multimodal imaging, 94.9% had three or more fea-tures of neovascular AMD seen on OCTA. In contrast, 90.5% of eyes that did not require treatment had fewer than three features.6

Monitoring Progress of AMDOCTA is useful in monitoring changes to CNV le-

sion characteristics following the initiation of treat-ment. The fine vessels exhibit attenuation, together with a reduction in total lesion area.7,8

POLYPOIDAL CHOROIDAL VASCULOPATHY

Currently, ICGA is the gold standard for diagnosis of polypoidal choroidal vasculopathy (PCV).9-11 Al-though the ICGA diagnostic criteria of PCV and base-line characteristics have been well-described,9-11 there are only a few reports of the features of PCV seen on OCTA.4,12-16

Detection of PolypsCompared with ICGA as the gold standard, the

polyps are detected on OCTA in 50% to 85% of eyes, respectively.13,15 The polyps were located beneath the retinal pigment epithelium (RPE)13,15 and have variable appearances on OCTA. Some polyps appear as areas of high flow signal,14,16 whereas others have reduced flow or hypoflow. In addition, in one study, a hypo-intense halo was reported surrounding the area of increased flow.16 In general, between 25% to 50% of eyes have high flow signal, whereas reduced flow signal was re-ported in 75% of eyes.16

Detection of Branching Vascular NetworkThe branching vascular network (BVN) has been

reported to be seen on OCTA in 70% to 100% of eyes and is located between the RPE and Bruch’s mem-brane.13,14 Using OCTA, BVN appears clearer com-pared to ICGA, and various morphologic patterns have been described, such as seafan or medusa.15

DIABETIC RETINOPATHY AND DIABETIC MACULAR EDEMA

Diabetes mellitus causes microvascular changes in the retina, which manifests as diabetic retinopathy (DR) and diabetic macular edema (DME). Although OCT is useful in assessing the location, pattern, and

extent of retinal edema, as well as detecting the pres-ence of intraretinal fluid, it does not provide informa-tion on the perfusion of the retina. Currently, FA is required to assess the microvascular changes caused by diabetes, such as capillary dropout, enlargement of the foveal avascular zone (FAZ), microaneurysms, and the presence of retinal neovascularization.

MicroaneurysmsMicroaneurysms are a hallmark of DR and appear

as pinpoint areas of hyperfluorescence on FA. Using OCTA (Figure 2), microaneurysms appear as focally dilated saccular or fusiform capillaries.17 The microan-eurysms have been reported to occur in both the super-ficial and deep capillary plexuses,18 although they are more numerous in the deep capillary plexus (Figure 2B).17-20 There is incomplete agreement in detection of microaneurysms using FA and OCTA — lesions that are detected using FA may not be seen on OCTA scans, and vice versa.17,19 In one study, it was reported that 62% of microaneurysms detected on FA were visual-ized on OCTA, with a mean of 7.3 microaneurysms per eye on OCTA compared to 11.7 on FA.19

Microvascular ChangesPatients with diabetes manifest with microvascular

changes on OCTA,17,19,21-23 even in eyes without clini-cally evident DR.21 Eyes with DR have reduced para- and perifoveal vessel density, with capillary dropout (Figure 2) and increased spacing between the large ves-sels.17,19,21,23 In addition, vascular abnormalities such as clustered capillaries, dilated capillary segments, tortuous vessels, reduced capillary density, intrareti-nal microvascular abnormalities, and retinal neovas-cularization have been detected using OCTA.21 OCTA has been reported to be superior to FA in characteriz-ing microvascular changes, in particular the boundar-ies of areas of ischemia. Using FA, masking may occur from fluorescein dye leakage in the intermediate and late phases of the angiogram.19,24,25

Foveal Avascular ZoneEyes with DR have a larger FAZ area and maximum

FAZ diameter compared to normal controls when mea-sured using OCTA (Figure 2). This was found in both the superficial and deep retinal plexuses.22,23 OCTA was closely correlated to FA findings in terms of FAZ parameters such as size, outline, and loss of perifoveal capillaries.22-24 An assessment of the FAZ parameters, however, should take into account the wide variation in FAZ parameters among normal eyes.26-29 The mean FAZ size has been reported to vary from 0.04 mm2 to 0.48 mm2 in the superficial plexus and 0.10 mm2 to 0.70 mm2 in the deep retinal plexus26 and is influenced

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by factors such as the central subfield retinal thick-ness,26,27 sex,26,29 and choroidal thickness.26

CONCLUSION

OCTA is a useful investigation that helps in the diagnosis, monitoring, and management of common retinal diseases. Its role will increase as advances con-tinue to be made in imaging techniques and process-ing algorithms.

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Colin S. Tan, MBBS, MMed (Ophth), FRCSEd (Ophth), can be reached at National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore; email: Colintan_eye@yahoo.com.sg.

Louis W. Lim, MBBS, can be reached at National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore; email: limwy1987@gmail.com.

SriniVas R. Sadda, MD, can be reached at Doheny Eye Institute, University of California Los Angeles, 1450 San Pablo St # 3000, Los Angeles, CA 90033; email: ssadda@doheny.org.

Seenu M. Hariprasad, MD, can be reached at the Department of Ophthalmology and Visual Science, University of Chicago, 5841 S. Maryland Avenue, MC2114, Chicago, IL 60637; email: retina@uchicago.edu.

Disclosures: Dr. Tan receives research funding from the National Medical Research Council Transition Award (NMRC/TA/0039/2015) and travel sup-port from Bayer, Heidelberg Engineering, and Novartis. Dr. Lim has no finan-cial disclosures. Dr. Sadda serves as a consultant for Allergan, Genentech, Roche, Regeneron, Alcon, Bausch & Lomb, Optos, and Carl Zeiss Meditec. He also receives research support from Allergan, Genentech, Optos, and Carl Zeiss Meditec. Drs. Tan, Lim, and Sadda have no financial or proprietary interests in the subject of this manuscript. Dr. Hariprasad is a consultant for Alcon, Allergan, Bayer, OD-OS, Clearside Biomedical, Ocular Therapeutix, Janssen, Leica, Spark, and Regeneron.